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The good news is that simply gene exchange may not cause H5N1 to trigger a pandemic. The bad news is that there are other ways that it could evolve into a pandemic virus. Nature story on bird flu ferret experimentNature 442, 490-491(3 August 2006) | doi:10.1038/442490b; Published online 2 August 2006

Researchers have tried to create a pandemic H5N1 influenza strain — and failed. Simply mixing genes from an H5N1 bird-flu strain with those from an H3N2 human strain did not result in a strain that was readily transmissible, at least among ferrets. The scientists who conducted the work, at the Centers for Disease Control and Prevention (CDC) in Atlanta, Georgia, say it suggests that the H5N1 virus will require a complex series of genetic changes to evolve into a pandemic strain. "These data do not mean that H5N1 cannot convert to become transmissible from person to person," says Julie Gerberding, director of the CDC. "We are not out of the woods on pandemic preparedness yet." Others agree, pointing out that there are many ways a pandemic strain could evolve. For instance, strains other than those used in the experiments could get together. "They need to look at other viruses, because both human and avian flu continue to evolve," says Frederick Hayden, a flu specialist at the University of Virginia, Charlottesville, who is currently working with the World Health Organization. Since 1997, millions of domestic and wild birds have died owing to the H5N1 strain of flu. It has infected at least 232 people and killed 134 of them. Scientists are worried that H5N1 will learn to pass easily between humans and kill millions more. In 1957 and 1968, pandemic strains of flu seem to have emerged when bird and human flu viruses exchanged genes, allowing the bird-flu virus to be easily transmitted between people. To test whether H5N1 might do easily to others. And even if they did pass on the virus, the other ferrets did not become fatally ill. The findings seem to indicate that the recombined viruses were less deadly than the original H5N1 strain and unlikely to transfer to other animals, the scientists say. They hope to repeat the experimentsthis, the CDC scientists used a technique called reverse genetics to snip genes out of H3N2 and H5N1 viruses and recombine them into hybrid bird–human viruses. They infected ferrets with the hybrids and tested whether the animals got sick and transferred the viruses to other ferrets (T. R. Maines et al. Proc. Natl Acad. Sci. USA doi:10/1073/ pnas.0605134103; 2006). Ferrets infected with hybrid viruses did not get as sick as those infected with the original H5N1 virus. In addition, the ferrets did not pass the hybrid virus to test the pandemic potential of other viruses — including those taken from patients after 1997, the year that the H5N1 strain they used was isolated. "We believe this model is a good tool to assess the potential of H5N1 viruses to cause a pandemic in the future," says Jacqueline Katz of the CDC, who led the work. Many questions remain unanswered, however. The ferret model may not perfectly replicate human disease, say scientists not involved in the experiments. Nor does the study address whether H5N1 could evolve into a pandemic strain by accumulating mutations if it passed through many people. It also did not test hybrids with human flu viruses other than H3N2. "The attention being paid to pandemic preparedness is certainly appropriate, and the results shouldn't dissuade people from continuing to progress in that area," says Hayden.